title: Pharmacokinetics of cefpodoxime in plasma and subcutaneous fluid following oral administration of cefpodoxime proxetil in male beagle dogs.
abstract: Pharmacokinetics of cefpodoxime in plasma (total concentration) and subcutaneous fluid (free concentration using microdialysis) was investigated in dogs following single oral administration of prodrug cefpodoxime proxetil (equivalent to 5 and 10 mg/kg of cefpodoxime). In a cross over study design, six dogs per dose were utilized after a 1 week washout period. Plasma, microdialysate, and urine samples were collected upto 24 h and analyzed using high performance liquid chromatography. The average maximum concentration (C(max) ) of cefpodoxime in plasma was 13.66 (±6.30) and 27.14 (±4.56) μg/mL with elimination half-life (t(1/2) ) of 3.01 (±0.49) and 4.72 (±1.46) h following 5 and 10 mg/kg dose, respectively. The respective average area under the curve (AUC(0-∞) ) was 82.94 (±30.17) and 107.71 (±30.79) μg·h/mL. Cefpodoxime was readily distributed to skin and average free C(max) in subcutaneous fluid was 1.70 (±0.55) and 3.06 (±0.93) μg/mL at the two doses. Urinary excretion (unchanged cefpodoxime) was the major elimination route. Comparison of subcutaneous fluid concentrations using pharmacokinetic/pharmacodynamic indices of fT(>MIC) indicated that at 10 mg/kg dose; cefpodoxime would yield good therapeutic outcome in skin infections for bacteria with MIC(50) upto 0.5 μg/mL while higher doses (or more frequent dosing) may be needed for bacteria with higher MICs. High urine concentrations suggested cefpodoxime use for urinary infections in dogs.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
authors.forename: V
authors.initials: V
authors.lastname: Kumar
authors.forename: R
authors.initials: R
authors.lastname: Madabushi
authors.forename: M B B
authors.initials: MB
authors.lastname: Lucchesi
authors.forename: H
authors.initials: H
authors.lastname: Derendorf
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D015296:Ceftizoxime / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D018592:Cross-Over Studies; D004285:Dogs / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D007279:Injections, Subcutaneous / Q000662:veterinary; D008297:Male; D011897:Random Allocation; D000097623:Cefpodoxime; D000097627:Cefpodoxime Proxetil
chemical_list: D000900:Anti-Bacterial Agents; D015296:Ceftizoxime; D000097623:Cefpodoxime; D000097627:Cefpodoxime Proxetil